Why 1 in 5 cancer clinical trials fizzle

Why 1 in 5 cancer clinical trials fizzle

"Clinical trials are the scientific soul of cancer-cure advances, but nearly 20 percent of these publicly funded studies fail to draw enough patients to render verdicts on experimental therapies, investigators reported Tuesday.

That failure rate represents stalled progress in the pursuit of better cancer drugs and techniques – and “a waste of scarce human and economic resources,” according to a study by Fred Hutchinson Cancer Research Center and the University of Washington.


The Hutch researchers found that 18 percent of cooperative-group-sponsored trials closed due to low patient-accrual rates – or were accruing at less than 50 percent of the targeted participation number three or more years after launch.


Scientists already struggle to convince cancer patients to join clinical trials. Nationally, only 3 to 5 percent of adult cancer patients enroll in these studies.


And, then, there are highly motivated patients, like Wendy Ramsey, 60, diagnosed with chronic lymphocytic leukemia (CLL).

To combat her disease, Ramsey participated in four different trials. Today, she’s nearly four years into a Phase 1 clinical trial initially conducted through Fred Hutch to test a new treatment.

“It has been so very successful for me, I am generally in awe of my life these days,” said Ramsey, who lives in Idaho.

For that trial, she takes three pills daily with no detectable side effects, she said. She cycles, hikes and travels. Her doctor has told her she is in remission.

“As the months roll by, I sometimes stop and remember that I am a cancer patient,” Ramsey said. “Life is that normal. The trial is life changing for me.”

To teach herself how to find and review trials, she painstakingly tapped an online community of CLL patients.

“It taught me that cancer treatment is always a risk-versus-reward decision,” Ramsey said. “… It showed me that cancer patients live in a world with a very high level of hope – because we have to.”


“It is well documented that patients on clinical trials have better outcomes than those who do not participate,” Raghavan wrote. “… We should strive to improve trial enrollment, giving the associated potential for improved results.” :



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10 Replies

  • Happy new year Neil. Thanks for all that you do.


  • To me the 'sweet spot' in clinical trial is Phase 2. Phase 1 has a lot of risk (dosage escalation until unacceptable side effects) and Phase 3 is worthless (what sick cancer patient wants to risk getting a placebo?). I support getting rid of all Phase 3 trials so patients can get live-saving drugs sooner.

  • An interesting and thought provoking question, especially as in rarer cancers it can be very difficult to get a drug into phase 3 trial because of population size.

    I think many here could answer for you why they have taken part in phase 3 trials from their own experience of need and rolling the Dice.

    The quote above is an unfortunate truth “It taught me that cancer treatment is always a risk-versus-reward decision,” Ramsey said. “… It showed me that cancer patients live in a world with a very high level of hope – because we have to.”

    Excerpts from the CLLSA clinical trials website pages:


    We have moved from the times when the only treatment intent was palliation to a time when real efforts at achieving meaningful improvements in survival can be expected. There is the hope that in the not to distant future we may even talk of cure (or at least indefinite control) of CLL in more than just a small minority of patients. CLL is now arguably one of the most rapidly moving disorders, in terms of our understanding, in oncology generally. Along with these advances come many challenges including how do we test the variety of therapeutic options for patients and therefore navigate our way to the most effective treatment for individual patients? How do haematologists who do not have a particular specialist interest in CLL maintain and update their knowledge in order to deliver the best therapy for their patients? In addition, how do we make available these advances in our understanding of the biology of CLL to all patients in the United Kingdom? The new treatments for CLL are not inexpensive both in terms of financial implications to the NHS as well as in terms of potential side effects for individual patients.

    The answer to all of these questions must be, at least in part, by continuing our strong commitment to well designed clinical trials. However there are significant obstacles placed in our way with increasing bureaucracy, increasing costs of running trials and the not inconsiderable cost of the newer agents even within clinical trials.


    There is a very active CLL trials group in the United Kingdom which has a track record of performing innovative clinical trials. Clinical trials are the bed-rock of evidence-based medicine and are essential if we are to continue the progress currently being made in CLL and other diseases. The most important people in the trials are the patients as they are trusting us to develop sensible well-designed trials which give them the best possible care and hopefully advance our understanding of CLL for future generations of patients.

    Read the full article about CLL trials in the UK cllsupport.org.uk/article/c...

    Phase 3 trials test whether a “newer” treatment (a new drug or combination of drugs) is better than the current standard, by comparing the group being treated with the new medicine against a group being treated with the existing treatment (A trial is normally randomized between the new regime and the standard) , although promising treatments may emerge in other phases, those trials may not be definitive enough to provide robust enough data to change the way patients are treated or the standard of care.

    Hope is a big part of any cancer treatment and participating in a randomised phase 3 trial offers hope for those wishing to receive a new drug when there may be no other route to access. Drugs reaching phase 3 trials provide most evidence of safety and efficacy. Phase 2 trials can provide an earlier access route to those not wishing to be randomised. Patients are needed in all trial phases of an experimental drug to ensure progress is made and if improved efficacy is proven it reaches the population.

    More cross over potential in phase 3 clinical trial design would be my suggestion

    Happy New Year


  • No phase 3 clinical cancer trial gives placebos only as treatment these days, at least not CLL trials. One arm of trial is a current approved treatment and other is a new drug. On trials using a combination of drugs, there may be a standard treatment plus a new drug, and a standard treatment plus a placebo, so the worse the patient gets is a standard treatment.

  • Hi KC1953. If you search clinicaltrials.gov for Phase 3 AND placebo you'll find current and completed trials. We turned down NCT01732913 (that is still recruiting) because of the placebo.

  • I do not believe any of the recently started trials work that way. Most well known investigators would not want to be associated with that practice. If new trials are created with only a placebo as treatment that is immoral.

  • Several trials for CLL treatments have been suggested to me in the last year (by Prof Hillmen in Leeds). None of them have involved placebos.

  • Placebos are rarely given in CLL trials, so KC1953's stance is understandable but you've happened across one where this is the case:


    "A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas"

    So most unusually in this trial, you are randomly assigned to a group that will get Rituximab and a placebo or Rituximab and Idelalisib. Given Rituximab monotherapy is far less effective than other current CLL treatments, you would hope that those in the Rituximab plus placebo arm would be allowed to swap to the Rituximab and Idelalisib arm if that arm is shown to be far superior. This type of switch was allowed on a recent CLL trial, but you were wise to investigate the trial conditions thoroughly.


  • My point was that placebos are never give as the only treatment but are sometimes given with an approved treatment. The OP made it sound like he might end up only with a placebo and nothing else. Worst case he would have received idelalisib. I stand by my original response.

  • Yes kc1953 you are right to make this clear, I guess the devil is in the detail of this trial as it can be in any other. This trial is for patients with Follicular lymphoma (FL), Small lymphocytic lymphoma (SLL), Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM) & Marginal zone lymphoma (MZL)

    I see that the Placebo Comparator arm is: Rituximab+Placebo and there is a provision should a person not respond to rituximab:

    "Following confirmation of iNHL disease progression by the independent review committee and unblinding, participants may be eligible to receive open-label idelalisib 150 mg twice daily."

    If I remember correctly the CLL equivalent of this trial NCT01539512 was of similar design and did not include this provision , but was concluded early and unblinded to enable crossover of all patients to idelalisib, The CLL trial results were published in the New England Journal nejm.org/doi/full/10.1056/N... this data is what has enabled health authorities to approve the drug for NHS use to treat CLL here in the UK

    I am not a medic and don't know too much about iNHLs other than SLL, but hope this combination proves as successful in SLL, FL, MZL, & LPL/WM as it has in CLL


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